Current advances in pain regimens for percutaneous nephrolithotomy A comprehensive review.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) causes pain and discomfort after surgery. The primary causes of immediate postoperative pain after PCNL are visceral pain from the ureters and kidneys, and body surface discomfort from incisions. Acute, untreated pain has the potential to develop into chronic pain, which remains a considerable burden for the rehabilitation of patients. The goal of this review was to describe the current options for treating pain post-PCNL. METHODS: We conducted a literature review of all published manuscripts on pain protocols for patients undergoing PCNL and related topics; 50 published manuscripts were identified and reviewed. RESULTS: PCNL morbidity must be reduced by an appropriate management of postoperative pain. Opioids, multimodal therapy, tubeless PCNL, reduced size of nephrostomy tube, and regional anesthesia are currently available for reducing postoperative pain. CONCLUSIONS: Implementing successful treatment strategies for postoperative pain after PCNL is key in reducing the morbidity and mortality of PCNL.

Social exercise interventions for children who have complex developmental needs: A systematic review.

Exercise interventions are identified as effective treatments for children not meeting developmental milestones. This systematic review synthesizes research regarding exercise interventions that involved social participatory elements, for children with complex developmental needs. Academic Search Complete, CINAHL, Emcare, Proquest Theses and Dissertations, MEDLINE, and Google Scholar were searched systematically for relevant studies. Peer-reviewed studies meeting the review aim and published between 2000 and 2021 in English, were included. Methodological quality of 49 eligible studies (47 controlled trials, two mixed methods, total of 2355 participants) was appraised using the Mixed Methods Appraisal Tool. Narrative synthesis identified two groups of studies: Group 1 incorporated intentional social participatory elements; Group 2 likely involved incidental social participation. Most studies were of moderate to low methodological quality. Few measured impacts of interventions upon total physical activity levels. Short-term improvements in physical outcomes - particularly motor skills - were most frequently reported and were the main benefit of social exercise interventions for children with complex developmental needs, for which evidence exists. Further rigorous, longitudinal research is needed to assess social, psychological, and executive function outcomes of social exercise interventions in this population. Such interventions should incorporate booster sessions to provide children with greater opportunity to meet developmental milestones.

Bacteriophage-host interactions in Streptococcus thermophilus and their impact on co-evolutionary processes.

Bacteriophages (or phages) represent a persistent threat to the success and reliability of food fermentation processes. Recent reports of phages that infect Streptococcus thermophilus have highlighted the diversification of phages of this species. Phages of S. thermophilus typically exhibit a narrow range, a feature that is suggestive of diverse receptor moieties being presented on the cell surface of the host. Cell wall polysaccharides, including rhamnose-glucose polysaccharides and exopolysaccharides have been implicated as being involved in the initial interactions with several phages of this species. Following internalization of the phage genome, the host presents several defences, including CRISPR-Cas and restriction and modification systems to limit phage proliferation. This review provides a current and holistic view of the interactions of phages and their S. thermophilus host cells and how this has influenced the diversity and evolution of both entities.

Predictive value of high-sensitivity troponin for significant coronary artery disease in new-onset atrial fibrillation with rapid ventricular response.

BACKGROUND: High-sensitivity troponin-T (HS-cTnT) levels are often measured in patients presenting with atrial fibrillation (AF), with many subjected to unnecessary invasive assessments. The significance of a normal or mildly raised HS-cTnT in this context is poorly understood. This study aimed to determine the predictive value of HS-cTnT for significant coronary artery disease (CAD) in new AF with rapid ventricular response. We also compared the discriminative ability of HS-cTnT to suspected angina for significant CAD. METHODS: We examined patients presenting with new AF to two tertiary Irish centers in a defined period. Those included had HS-cTnT taken at presentation and subsequent ischemic evaluation. RESULTS: Of 5350 cases screened for inclusion, 281 were deemed eligible. Of these, 148 and 133 patients had a positive and negative index HS-cTnT, respectively. Of those with negative HS-cTnT, 13 (9.8%) had significant CAD versus 51 (34.5%) with positive HS-cTnT (P < 0.001). Positive Hs-cTnT status remained significant upon multivariate analysis (OR, 2.9; 95% CI, 1.37-6.14; P = 0.005). A similar model where HS-cTnT was replaced with suspected angina produced an OR of 1.64 (95% CI, 0.75-3.59; P = 0.213). A logistic model determined optimal cutoff value for HS-cTnT to be less than 30 ng/l, producing a negative predictive value of 91.8% and area under the receiver operative curve of 83.36. CONCLUSION: HS-cTnT exhibits potential as an effective screening biomarker to predict nonsignificant CAD in new rapid AF, allowing more targeted and rationalized ischemic testing. HS-cTnT may also be a more accurate predictor of significant CAD than clinically suspected stable angina.Graphical abstract: http://links.lww.com/MCA/A540.

Issues for recruitment and retention of clinical research professionals at academic medical centers: Part 1 - collaborative conversations Un-Meeting findings.

Background: Identification of evidence-based factors related to status of the clinical research professional (CRP) workforce at academic medical centers (AMCs) will provide context for National Center for Advancing Translational Science (NCATS) policy considerations and guidance. The objective of this study is to explore barriers and opportunities related to the recruitment and retention of the CRP workforce. Materials and Methods: Qualitative data from a series of Un-Meeting breakout sessions and open-text survey questions were analyzed to explore barriers and recommendations for improving AMC CRP recruitment, retention and diversity. Results: While certain institutions have established competency-based frameworks for job descriptions, standardization remains generally lacking across CTSAs. AMCs report substantial increases in unfilled CRP positions leading to operational instability. Data confirmed an urgent need for closing gaps in CRP workforce at AMCs, especially for attracting, training, retaining, and diversifying qualified personnel. Improved collaboration with human resource departments, engagement with principal investigators, and overcoming both organizational and resource challenges were suggested strategies, as well as development of outreach to universities, community colleges, and high schools raising awareness of CRP career pathways. Discussion: Based on input from 130 CRP leaders at 35 CTSAs, four National Institute of General Medical Sciences' Institutional Development Award (IDeA) program sites, along with industry and government representatives, we identified several barriers to successful recruitment and retention of a highly trained and diverse CRP workforce. Results, including securing institutional support, champions, standardizing and adopting proven national models, improving local institutional policies to facilitate CRP hiring and job progression point to potential solutions.

Rare Mental Health Disorders Affecting Urologic Care: A Comprehensive Review.

Management of mental health illnesses and needs are important in fostering psychosocial support, interprofessional coordination, and greater adherence to treatment protocols in the field of urology. This can be especially true for mental health conditions that may greatly impact the presentation of a patient in the healthcare setting with urologic symptoms. This review describes the history, epidemiology, pathophysiology, clinical presentation, and treatment of somatic symptom disorder, illness anxiety disorder, compulsive sexual behavior/hypersexuality, factitious disorder, malingering symptoms, and conversion disorder in the realm of urology. Given the newly updated psychiatric diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, there has been a lack of studies reviewing how these illnesses may present in a urology patient encounter. Additionally, as these mental health illnesses may carry a rare incidence compared to other well-known mental health illness such as generalized depression or generalized anxiety disorder, we have found that the lack of provisions and recognition of the diseases can prolong the timeline for diagnosis and lead to an increased cost in both healthcare and quality of life of patients with these mental health illnesses. This review provides awareness on these mental health conditions which may greatly impact patient history and presentation within the field of urology. Additionally, urologic care providers may have an improved understanding of interdisciplinary management of such illnesses and the common symptoms patients may present with such diseases.

Framework for creating an incident command center during crises.

The Hospital Incident Command System (HICS) is an incident management system specific to hospitals based on the principles of Incident Command System (ICS), and it includes prevention, protection, mitigation, response, and recovery. It plays a crucial role in effective and timely response during the periods of disasters, mass casualties, and public health emergencies. In recent times, hospitals have used a customized HICS structure to coordinate effective responses to public health problems such as the Ebola outbreak in the US and SARS epidemic in Taiwan. The current COVID-19 pandemic has placed unprecedented challenges on the healthcare system, necessitating the creation of HICS that can help in the proper allocation of resources and ineffective utilization of healthcare personnel. The key elements in managing a response to this pandemic include screening and early diagnosis, quarantining affected individuals, monitoring disease progression, delivering appropriate treatment, and ensuring an adequate supply of personal protective equipment (PPE) to healthcare staff.

Adjuvant Drugs for Peripheral Nerve Blocks: The Role of NMDA Antagonists, Neostigmine, Epinephrine, and Sodium Bicarbonate.

The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes.

The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence.

Adaptation to changing environments and immune evasion is pivotal for fitness of pathogens. Yet, the underlying mechanisms remain largely unknown. Adaptation is governed by dynamic transcriptional re-programming, which is tightly connected to chromatin architecture. Here, we report a pivotal role for the HIR histone chaperone complex in modulating virulence of the human fungal pathogen Candida albicans. Genetic ablation of HIR function alters chromatin accessibility linked to aberrant transcriptional responses to protein as nitrogen source. This accelerates metabolic adaptation and increases the release of extracellular proteases, which enables scavenging of alternative nitrogen sources. Furthermore, HIR controls fungal virulence, as HIR1 deletion leads to differential recognition by immune cells and hypervirulence in a mouse model of systemic infection. This work provides mechanistic insights into chromatin-coupled regulatory mechanisms that fine-tune pathogen gene expression and virulence. Furthermore, the data point toward the requirement of refined screening approaches to exploit chromatin modifications as antifungal strategies.

Lamotrigine and Stevens-Johnson Syndrome Prevention.

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.

Comparison of hospital course and outcome in hospital-acquired vs pre-existing delirium.

BACKGROUND: Delirium is a major source of morbidity in the inpatient hospital setting. This study examined differences between patients with delirium present prior to hospital admission and those with hospitalacquired delirium in several health outcomes. METHODS: A total of 12,529 patients on 2 inpatient units were included in this retrospective cohort study. Outcomes were assessed using chart review. Other variables were compared across groups and included in multivariate models predicting discharge location within the hospitalacquired delirium group. RESULTS: Of 709 patients with delirium, 83% had pre-admission prevalent and 17% had post-admission incident delirium. Compared with patients with preexisting delirium, patients with hospital-acquired delirium had greater hospital durations and mortality and were more likely to receive ICU care, more likely to receive multiple classes of medications, and less likely to be discharged home without home health services. Multivariate analysis in the hospital-acquired delirium group found that several variables independently predicted discharge location. CONCLUSIONS: Patients with hospital-acquired delirium had worse hospital outcomes and a more complicated hospital course than those with preexisting delirium. Administration of various medications, several demographic variables, and some hospital-related variables were independently associated with worse outcomes within the hospital-acquired delirium group. These results demonstrate that patients with hospitalacquired delirium are a vulnerable subgroup deserving special attention.

Extending borders of knowledge: gendered pathways to prison in Thailand for international cross border drug trafficking.

Few researchers have concerned themselves with qualitative gender-comparative studies of women's and men's prison trajectories - particularly appraisals relating to international cross border drug trafficking (ICBDT). Using life history interviews with prisoners incarcerated in three regions of Thailand, we describe, examine and compare the features of women's and men's pathways to prison for ICBDT. Overall, the findings point to both similarities and divergences in experiences by gender. Three pathways to prison emerged for both women and men: (1) 'deviant' lifestyle, (2) economic familial provisioning and (3) inexperience and deception. However, gendered variance was found within these pathways; an additional woman-only trajectory, the romantic susceptibility pathway, was also identified.

A Validation Study: How Predictive Is a Diagnostic Coding Algorithm at Identifying Rheumatic Heart Disease in Western Australian Hospital Data?

BACKGROUND: International Classification of Diseases codes for rheumatic heart disease (RHD) (ICD-10 I05-I08) include valvular heart disease of unspecified origin, limiting their usefulness for estimating RHD burden. An expert opinion-based algorithm was developed to increase their accuracy for epidemiological case ascertainment. The algorithm included codes not defaulting to RHD ('probable') plus selected codes pertaining to mitral valve involvement in patients <60 years ('possible'). We aimed to determine the positive predictive value (PPV) for RHD of algorithm-selected hospital admissions. METHODS: Chart reviews of RHD-coded admissions (n=368) to Western Australian tertiary hospitals (2009-2016) authenticated RHD diagnosis. We selected all cases with algorithm-positive codes from populations at high-risk of RHD and an age-stratified random sample from low-risk groups. RHD status was determined from echocardiographic reports or clinical diagnosis in charts. PPVs were compared by population risk status (high-risk/low-risk), age group, gender, principal/secondary diagnosis and probable/possible codes. RESULTS: High-risk patients had higher PPVs than low-risk patients (83.8% vs 54.9%, p<0.0001). PPVs were 91.5% and 51.5% respectively for algorithm-defined 'probable RHD' and 'possible' codes (p<0.0001). The PPVs in low-risk patients were higher for principal diagnoses than secondary diagnoses (84.5% vs 44.8%, weighted p<0.0001) but were similar in high-risk patients (92.5% vs 81.7%, p=0.096). CONCLUSION: The algorithm performs well for RHD coded as a principal diagnosis, 'probable' codes or in populations at high risk of RHD. Refinement is needed for identifying true RHD in low-risk groups.

Rheumatic heart disease in pregnancy: Profile of women admitted to a Western Australian tertiary obstetric hospital.

This retrospective study assessed maternal and perinatal outcomes for women with rheumatic heart disease (RHD) admitted to the largest tertiary obstetric hospital in Western Australia from 2009 to 2016. Of 54 women identified, 75.9% were Indigenous, 59.3% lived in rural areas and 40.7% had severe RHD. Heart failure developed in 10% who gave birth. Indigenous women were younger, had higher gravidity (P = 0.0305), were more likely to receive secondary prophylaxis (P = 0.0041) and have sub-optimal antenatal clinic attendance (P = 0.0078). There were no maternal deaths and two perinatal deaths (4.0%), reflecting vigilance in the obstetric management of women with RHD in Western Australia.

High-sensitivity troponin assays: development and utility in a modern health-care system.

Introduction: The introduction of cardiac troponin (cTn) assays have revolutionized the diagnosis and management of acute myocardial infarction in Emergency Departments worldwide. Its success has led to significant research and development investment in this area culminating in the development of newer high-sensitivity cardiac troponin assays (hs-cTn). While these newer assays allow for more rapid diagnosis by decreasing the time interval between serial data points, there is an inevitable trade off between increasing sensitivity and specificity. This review examines in detail the introduction and implementation of hs-cTN and its implications for clinical practice.Areas covered: This article reviews the history and development of high-sensitivity troponin assays and their application to clinical practice and current evidence base. It also discusses both the positive and negative aspects of the continuing increasing sensitivity of biochemical assays and the translation of this into clinical practice. Potential future developments are also discussed.Expert commentary: It is clear that there are many benefits to detecting extremely low concentration of cardiac troponin including the development of rapid rule out algorithms and the cost and time-saving advantages associated with the quicker movement of patients through the health-care system. It is important to note however that detecting troponin at very low concentrations also dramatically increases the false-positive rates and leads to a potentially large increase in invasive testing and diagnosis of myocardial infarction.

Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe.

BACKGROUND: Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. This study aims to characterise the manner in which this microbe may modulate host bile pool composition and immune response, in the context of cardiovascular disease. Lactobacillus mucosae DPC 6426 was assessed for bile salt hydrolase activity and specificity. The microbe was compared against several other enteric strains of the same species, as well as a confirmed bile salt hydrolase-active strain, Lactobacillus reuteri APC 2587. RESULTS: Quantitative bile salt hydrolase assays revealed that enzymatic extracts from Lactobacillus reuteri APC 2587 and Lactobacillus mucosae DPC 6426 demonstrate the greatest activity in vitro. Bile acid profiling of porcine and murine bile following incubation with Lactobacillus mucosae DPC 6426 confirmed a preference for hydrolysis of glyco-conjugated bile acids. In addition, the purified exopolysaccharide and secretome of Lactobacillus mucosae DPC 6426 were investigated for immunomodulatory capabilities using RAW264.7 macrophages. Gene expression data revealed that both fractions stimulated increases in interleukin-6 and interleukin-10 gene transcription in the murine macrophages, while the entire secretome was necessary to increase CD206 transcription. Moreover, the exopolysaccharide elicited a dose-dependent increase in nitric oxide and interleukin-10 production from RAW264.7 macrophages, concurrent with increased tumour necrosis factor-α secretion at all doses. CONCLUSIONS: This study indicates that Lactobacillus mucosae DPC 6426 modulates both bile pool composition and immune system tone in a manner which may contribute significantly to the previously identified cardio-protective phenotype.

Correlation of Trace Silicone Contamination Analyses on Epoxy Composites Using X-ray Photoelectron Spectroscopy (XPS) and Laser-Induced Breakdown Spectroscopy (LIBS).

Surface treatment and surface characterization techniques are critical to ensure that adherends are chemically activated and free of contaminants before adhesive bonding. Silicone contamination from mold release agents and other sources can interfere with interfacial bonding, decreasing the durability and performance of bonded composite structures. It is necessary to have tools and methods that can be used in a production environment to reliably detect low levels of contaminants in a rapid, simple, and cost-effective manner to improve bond reliability. In this work, surface characterization of carbon fiber reinforced polymer (CFRP) composites with epoxy matrix was performed using laser-induced breakdown spectroscopy (LIBS), and the results were compared with those obtained from X-ray photoelectron spectroscopy (XPS). Laser-induced breakdown spectroscopy offers many advantages over XPS in terms of ease of use, sample preparation, and real-time results. The objective of the comparison was to study the sensitivity of LIBS and to investigate the quantification of the surface species measured by LIBS. Another objective was to assess the reliability of each technique for surface contaminant characterization. The as-processed CFRP panels had trace surface silicone contamination from the fabrication process, the source of which was not investigated. The composites were laser treated at select average laser power levels, resulting in varying levels of contamination reduction. The Si atomic percentage measurements using XPS were conducted on both control and laser-ablated surfaces. The results showed an excellent correlation in Si concentration between the two techniques.

The changing face of cancer treatments.

This case demonstrates the effectiveness and ongoing potential of novel lung cancer therapies, specifically immunotherapy agents such as nivolumab, a T-cell programmed death 1 (PD-1) receptor inhibitor. In this case study, our patient had a significant burden of disease with nodal involvement above and below the diaphragm at the time of diagnosis. They were commenced on standard of care therapy: cisplatin and pemetrexed. Despite five cycles of treatment with these agents, their disease progressed significantly with the development of brain metastasis. The patient was switched to a novel immunotherapy agent, nivolumab, and had a complete response to it. Currently, there is no active disease-the lymph nodes have all regressed, the brain metastases have disappeared (with the help of stereotactic surgery) and no further metastases have developed. The patient is tolerating the treatment well and has had no significant adverse reactions to the immunotherapy agent.

Differentiation of High-Grade Glioma and Intracranial Metastasis Using Volumetric Diffusion Tensor Imaging Tractography.

OBJECTIVE: A reliable, noninvasive method to differentiate high-grade glioma (HGG) and intracranial metastasis (IM) has remained elusive. The aim of this study was to differentiate between HGG and IM using tumoral and peritumoral diffusion tensor imaging characteristics. METHODS: A semiautomated script generated volumetric regions of interest (ROIs) for the tumor and a peritumoral shell at a predetermined voxel thickness. ROI differences in diffusion tensor imaging-related metrics between HGG and IM groups were estimated, including fractional anisotropy, mean diffusivity, total fiber tract counts, and tract density. RESULTS: The HGG group (n = 46) had a significantly higher tumor-to-brain volume ratio than the IM group (n = 35) (P < 0.001). The HGG group exhibited significantly higher mean fractional anisotropy and significantly lower mean diffusivity within peritumoral ROI than the IM group (P < 0.05). The HGG group exhibited significantly higher total tract count and higher tract density in tumoral and peritumoral ROIs than the IM group (P < 0.05). Tumoral tract count and peritumoral tract density were the most optimal metrics to differentiate the groups based on receiver operating characteristic curve analysis. Predictive analysis using receiver operating characteristic curve thresholds was performed on 13 additional participants. Compared with correct clinical diagnoses, the 2 thresholds exhibited equal specificities (66.7%), but the tumoral tract count (85.7%) seemed more sensitive in differentiating the 2 groups. CONCLUSIONS: Tract count and tract density were significantly different in tumoral and peritumoral regions between HGG and IM. Differences in microenvironmental interactions between the tumor types may cause these tract differences.

PCSK9 inhibitors and LDL reduction: pharmacology, clinical implications, and future perspectives.

INTRODUCTION: PCSK9 inhibitors are monoclonal antibodies to proprotein convertase-subtilisin/kexin type 9 which significantly reduce LDL cholesterol concentration in vivo by inhibiting degradation of the LDL receptor in hepatocytes. The introduction of PCSK9 inhibitors heralded a new era of intensive LDL-C reduction with LDL-C concentrations lowered below levels ever thought possible with conventional treatments such as statins. With their introduction considerations regarding cost, clinical outcomes and long-term safety are paramount. Areas covered: This review examines the pharmacology of PCSK9 inhibitors and summarizes the current evidence base for use in clinical practice from an efficacy, safety, and cardiovascular outcome perspective including recently presented data on alirocumab. It also examines the potential role of these agents into the future. Potential issues with PCSK9 inhibitors are examined and future pharmacologic targets are examined including siRNA and PCSK9 vaccination. Expert commentary: It is clear that the PCSK9 inhibitors are highly effective in the lowering of LDL cholesterol. However, this reduction comes at a large financial cost, and although early outcome data has been positive, the role of PCSK9 inhibition remains confined to limited patient groups at present. As more long-term data is gathered on clinical outcomes and safety, the role for these agents may expand.